This is a renewal application for the Hormones/Membranes Training Program. For the past ten years this program has provided multidisciplinary training at the doctoral and postdoctoral levels for research careers in the molecular biology and cell biology of hormones and receptors. Request is made for continued support of this program at the level of six predoctoral and two postdoctoral trainee positions. The training faculty, as a group, represent all levels of seniority and their research covers many of the important areas of hormone/receptor research ranging from basic cell biology to gene therapy. New directions in this application include a focus on molecular endocrinology including prohormone processing and trafficking, gene-targeting of hormone receptors and molecular mechanisms of tyrosine kinases. Our research interactions and the joint training of predoctoral and postdoctoral students lend themselves to a highly integrated and cohesive program. Through formal course work, participation in research seminars, and individual research projects, trainees develop the skills necessary for independent investigation. Specifically, research training is provided in three major areas which reflect the expertise and skills of the training faculty. These are: i. Polypeptide Hormones: Prohormone Processing, Regulation of Gene Expression, and Action (D. Shields, R.S. Zukin, L. Fricker, J. Kessler) ii. Membrane Receptors: Mutational Analysis, Gene-Targeting, and Regulation of expression (R.S. Zukin, T. Bargiello, N. Carrasco, J. Kessler, S. Moshe, C. Rubin) iii. Signal Transduction (J. Backer, J. Kessler, L. Marsh, C. Rubin, B. Satir) Predoctoral students will be required to hold a Bachelor's degree or equivalent. These trainees will carry out research projects under the supervision of one of the trainers and an advisory committee. Formal coursework and a qualifying exam are required. Predoctoral trainees will receive the Ph.D. degree in Anatomy & Structural Biology, Developmental & Molecular Biology, Molecular Pharmacology, and Neuroscience. Postdoctoral trainees (either M.D. or Ph.D.) engage in full-time research at an advanced level for one to three years in the laboratory of one of the trainers while interacting with other trainers. In addition, postdoctoral fellows will audit relevant graduate courses, participate in Work in Progress seminars, one or more Departmental journal clubs, and attend Ethics and Grant Writing Workshops. Application to the Hormones/Membranes Postdoctoral Training Program is a multi-staged process, involving 1) acceptance of the applicant by the potential mentor; 2) presentation of an informal seminar to the potential mentor; and 3) selection by the Steering Committee. This program allows both predoctoral and postdoctoral trainees to obtain multidisciplinary training in an area for which our institution has no other specific training grant support, namely the interaction of hormones and other effectors with membrane receptors and other membrane components.